論文

国際誌
2024年3月22日

Structure of the human Bre1 complex bound to the nucleosome.

Nature communications
  • Shuhei Onishi
  • ,
  • Kotone Uchiyama
  • ,
  • Ko Sato
  • ,
  • Chikako Okada
  • ,
  • Shunsuke Kobayashi
  • ,
  • Keisuke Hamada
  • ,
  • Tomohiro Nishizawa
  • ,
  • Osamu Nureki
  • ,
  • Kazuhiro Ogata
  • ,
  • Toru Sengoku

15
1
開始ページ
2580
終了ページ
2580
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41467-024-46910-8

Histone H2B monoubiquitination (at Lys120 in humans) regulates transcription elongation and DNA repair. In humans, H2B monoubiquitination is catalyzed by the heterodimeric Bre1 complex composed of Bre1A/RNF20 and Bre1B/RNF40. The Bre1 proteins generally function as tumor suppressors, while in certain cancers, they facilitate cancer cell proliferation. To obtain structural insights of H2BK120 ubiquitination and its regulation, we report the cryo-electron microscopy structure of the human Bre1 complex bound to the nucleosome. The two RING domains of Bre1A and Bre1B recognize the acidic patch and the nucleosomal DNA phosphates around SHL 6.0-6.5, which are ideally located to recruit the E2 enzyme and ubiquitin for H2BK120-specific ubiquitination. Mutational experiments suggest that the two RING domains bind in two orientations and that ubiquitination occurs when Bre1A binds to the acidic patch. Our results provide insights into the H2BK120-specific ubiquitination by the Bre1 proteins and suggest that H2B monoubiquitination can be regulated by nuclesomal DNA flexibility.

リンク情報
DOI
https://doi.org/10.1038/s41467-024-46910-8
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/38519511
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10959955
ID情報
  • DOI : 10.1038/s41467-024-46910-8
  • PubMed ID : 38519511
  • PubMed Central 記事ID : PMC10959955

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